Mutagenetix > Incidental Mutation

Incidental Mutation 'R9088:Mlkl'

690763

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.087) question?

Stock #

R9088 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

112038429-112064809 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 112049365 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Serine at position 253 (R253S)

Ref Sequence

ENSEMBL: ENSMUSP00000055521 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432]

AlphaFold

Q9D2Y4

PDB Structure

Structure of MLKL [X-RAY DIFFRACTION]
Crystal structure of the mouse MLKL kinase-like domain [X-RAY DIFFRACTION]
Crystal structure of the mouse RIP3-MLKL complex [X-RAY DIFFRACTION]

Predicted Effect

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: R253S

Domain	Start	End	E-Value	Type
low complexity region	109	115	N/A	INTRINSIC
Pfam:Pkinase_Tyr	195	448	2.7e-41	PFAM
Pfam:Pkinase	200	450	2.1e-30	PFAM
Pfam:Kinase-like	270	438	1.6e-7	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000120432
AA Change: R253S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: R253S

Domain	Start	End	E-Value	Type
low complexity region	109	115	N/A	INTRINSIC
Pfam:Pkinase_Tyr	195	453	3.3e-42	PFAM
Pfam:Pkinase	196	453	1.4e-33	PFAM
Pfam:Kinase-like	270	438	8.9e-8	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to lack protein kinase activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (Rip3), which is a key signaling molecule in necroptosis pathway. Knockout of this gene in mice showed that it is essential for necroptosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit imapired macrophage and mouse embryonic fibroblast necroptosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ak9	A	G	10: 41,282,870 (GRCm39)	Y1212C		Het
Asah2	T	C	19: 32,030,360 (GRCm39)	Q104R	probably damaging	Het
Bnipl	T	A	3: 95,158,295 (GRCm39)	R9*	probably null	Het
Bpifa3	A	C	2: 153,975,685 (GRCm39)	N85T	possibly damaging	Het
C6	T	C	15: 4,792,956 (GRCm39)	Y354H	probably damaging	Het
Caln1	A	T	5: 130,443,617 (GRCm39)		probably benign	Het
Capn3	T	C	2: 120,321,451 (GRCm39)	F378L	probably benign	Het
Car6	T	C	4: 150,281,806 (GRCm39)	H125R	probably damaging	Het
Ccdc110	G	A	8: 46,394,882 (GRCm39)	E258K	probably damaging	Het
Cep295	C	A	9: 15,233,815 (GRCm39)	R2327L	probably benign	Het
Col14a1	T	A	15: 55,226,923 (GRCm39)	D224E	unknown	Het
Col16a1	T	A	4: 129,971,016 (GRCm39)	S938T	unknown	Het
Col4a2	A	G	8: 11,493,227 (GRCm39)	E1340G	possibly damaging	Het
Col6a6	C	T	9: 105,661,276 (GRCm39)	V278M	probably damaging	Het
Crybg2	T	A	4: 133,799,890 (GRCm39)	L41Q	probably damaging	Het
Ctss	A	T	3: 95,436,867 (GRCm39)	D50V	possibly damaging	Het
Ddx56	C	T	11: 6,209,612 (GRCm39)	A500T	probably benign	Het
Dmbt1	T	C	7: 130,718,418 (GRCm39)	V1713A	unknown	Het
Dnah1	T	C	14: 30,987,970 (GRCm39)	I3483V	probably benign	Het
E130308A19Rik	T	A	4: 59,737,594 (GRCm39)	F402I	probably benign	Het
Eml6	A	T	11: 29,768,424 (GRCm39)	H754Q	probably damaging	Het
Ern2	A	G	7: 121,772,890 (GRCm39)	Y576H	probably damaging	Het
Fat4	T	C	3: 39,061,448 (GRCm39)	S4344P	probably benign	Het
Fbxo40	A	G	16: 36,790,150 (GRCm39)	I320T		Het
Fbxw22	C	T	9: 109,207,952 (GRCm39)	D440N	probably damaging	Het
Fgd2	A	G	17: 29,583,913 (GRCm39)	E109G	probably damaging	Het
Gm19410	A	T	8: 36,240,766 (GRCm39)	D214V	probably damaging	Het
Hivep2	T	C	10: 14,006,995 (GRCm39)	Y1198H	probably damaging	Het
Itpr3	G	A	17: 27,337,651 (GRCm39)		probably benign	Het
Lrrc37	T	C	11: 103,511,762 (GRCm39)	K69E	unknown	Het
Lrrc8e	G	A	8: 4,284,410 (GRCm39)	V212M	probably damaging	Het
Map2	A	T	1: 66,453,773 (GRCm39)	S888C	probably damaging	Het
Met	G	T	6: 17,548,715 (GRCm39)	G920*	probably null	Het
Mmachc	T	A	4: 116,561,829 (GRCm39)	I102F	probably damaging	Het
Mnt	G	T	11: 74,733,880 (GRCm39)	V504L	unknown	Het
Mup14	C	T	4: 61,258,496 (GRCm39)	G96D	probably damaging	Het
Myh13	G	A	11: 67,242,885 (GRCm39)	E933K	probably damaging	Het
Ncoa6	A	G	2: 155,249,726 (GRCm39)	S1193P	probably damaging	Het
Nek10	T	C	14: 14,931,314 (GRCm38)	I762T	probably damaging	Het
Nmur1	G	T	1: 86,315,252 (GRCm39)	F204L	probably benign	Het
Or1ak2	A	G	2: 36,827,988 (GRCm39)	N286D	probably damaging	Het
Or52e15	G	T	7: 104,645,301 (GRCm39)	P270Q	probably damaging	Het
Or8a1	T	A	9: 37,641,806 (GRCm39)	I158F	probably damaging	Het
Pappa2	T	C	1: 158,763,927 (GRCm39)	Y528C	probably damaging	Het
Patl1	T	C	19: 11,920,289 (GRCm39)	S748P	possibly damaging	Het
Peg10	C	CTCA	6: 4,756,453 (GRCm39)		probably benign	Het
Polr1a	A	G	6: 71,908,767 (GRCm39)	T531A	probably benign	Het
Slit3	C	T	11: 35,012,463 (GRCm39)	S41F	possibly damaging	Het
Snap29	A	G	16: 17,246,058 (GRCm39)	Q226R	probably damaging	Het
Spmip2	G	A	3: 79,337,429 (GRCm39)	G185D	probably damaging	Het
Tmpo	A	G	10: 90,989,138 (GRCm39)		probably null	Het
Tnfrsf21	G	A	17: 43,348,607 (GRCm39)	G73E	probably damaging	Het
Tsc1	T	A	2: 28,552,617 (GRCm39)	C119S	possibly damaging	Het
Uox	A	G	3: 146,330,369 (GRCm39)	Y199C	probably damaging	Het
Vav2	T	C	2: 27,187,708 (GRCm39)	D231G	possibly damaging	Het
Vmn2r80	A	T	10: 79,005,378 (GRCm39)	K338N	probably benign	Het
Xylt2	G	A	11: 94,561,229 (GRCm39)	T178I	probably benign	Het
Zfp931	G	T	2: 177,709,594 (GRCm39)	T264K	probably damaging	Het
Zgrf1	A	G	3: 127,377,326 (GRCm39)	D857G	probably benign	Het

Other mutations in Mlkl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Mlkl	APN	8	112,046,060 (GRCm39)	nonsense	probably null
IGL01376:Mlkl	APN	8	112,046,379 (GRCm39)	missense	probably damaging	1.00
IGL02801:Mlkl	APN	8	112,043,064 (GRCm39)	missense	probably benign	0.18
IGL02965:Mlkl	APN	8	112,058,469 (GRCm39)	missense	probably benign	0.31
IGL03121:Mlkl	APN	8	112,041,612 (GRCm39)	missense	probably damaging	1.00
Ghoulish	UTSW	8	112,049,380 (GRCm39)	missense	probably damaging	1.00
mecro	UTSW	8	112,046,348 (GRCm39)	critical splice donor site	probably null
necro	UTSW	8	112,038,732 (GRCm39)	intron	probably benign
secro	UTSW	8	112,042,199 (GRCm39)	intron	probably benign
R0133:Mlkl	UTSW	8	112,054,580 (GRCm39)	missense	probably damaging	1.00
R0230:Mlkl	UTSW	8	112,041,694 (GRCm39)	missense	probably benign	0.07
R0387:Mlkl	UTSW	8	112,059,982 (GRCm39)	missense	probably damaging	1.00
R0497:Mlkl	UTSW	8	112,054,505 (GRCm39)	missense	probably damaging	1.00
R0735:Mlkl	UTSW	8	112,054,433 (GRCm39)	unclassified	probably benign
R1733:Mlkl	UTSW	8	112,049,380 (GRCm39)	missense	probably damaging	1.00
R1761:Mlkl	UTSW	8	112,060,355 (GRCm39)	missense	possibly damaging	0.81
R1911:Mlkl	UTSW	8	112,038,732 (GRCm39)	intron	probably benign
R2057:Mlkl	UTSW	8	112,060,242 (GRCm39)	missense	probably benign	0.07
R2921:Mlkl	UTSW	8	112,043,079 (GRCm39)	missense	probably benign	0.02
R3745:Mlkl	UTSW	8	112,042,199 (GRCm39)	intron	probably benign
R4760:Mlkl	UTSW	8	112,046,348 (GRCm39)	critical splice donor site	probably null
R5377:Mlkl	UTSW	8	112,054,569 (GRCm39)	missense	probably benign	0.23
R7052:Mlkl	UTSW	8	112,046,074 (GRCm39)	missense	possibly damaging	0.65
R7155:Mlkl	UTSW	8	112,046,035 (GRCm39)	missense	probably damaging	1.00
R7459:Mlkl	UTSW	8	112,060,162 (GRCm39)	missense	probably benign	0.36
R7728:Mlkl	UTSW	8	112,060,251 (GRCm39)	missense	probably damaging	1.00
R8036:Mlkl	UTSW	8	112,060,086 (GRCm39)	missense	probably damaging	1.00
R8064:Mlkl	UTSW	8	112,038,700 (GRCm39)	missense	probably benign	0.38
R9152:Mlkl	UTSW	8	112,046,403 (GRCm39)	missense	probably damaging	1.00
R9275:Mlkl	UTSW	8	112,043,055 (GRCm39)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- AAGCACAGCTCTCTAACCTCTTAAG -3'
(R):5'- TACAGCCAAGCCTGTCACTC -3'

Sequencing Primer
(F):5'- TTAAGCTCTCACCTGCAGATC -3'
(R):5'- CCTATACCAAGAGTCGCTGATGGTG -3'

Posted On

2021-12-30